The Pgbd5 DNA transposase is required for mouse cerebral cortex development through DNA double-strand breaks formation

Abstract

AbstractTransposons are conserved mobile genetic elements and one of the major sources of genetic variability during organisms’ evolution. PiggyBac Transposable Element Derived 5 (Pgbd5), an evolutionarily conserved vertebrate DNA transposase-coding gene, is highly expressed in the central nervous system during development and adult life, suggesting it may play a role in neuronal differentiation and maintenance.Here, we show thatPgbd5controls the expression of pro-neuronal and proliferative genes in a cell autonomous manner, leading to a decreased generation of neurons with altered migration. This activity depends on the induction of endogenous DNA double-strand breaks (DSBs).These results positionPgbd5as a crucial regulator of brain development through its endonuclease activity.One-Sentence SummaryPgbd5regulates cerebral cortex neurogenesis through DNA double-strand breaks modulation.